Epidermolysis bullosa (EB) represents a spectrum of conditions characterized by blistering and mechanical fragility of the skin. Individuals with EB display tremendous clinical diversity, as the dermal-epidermal basement membrane zone contains a number of specialized adhesive structures which links the basal epidermis cytoskeleton to the papillary dermis. The molecular basis of EB has been linked to 18 genes, leading to the classification of 28 clinical (15 EBS, 8 JEB, 14 DEB, 1 Kindler) EB subtypes and four major EB groups (Fine et al., JAAD June 2014). The EB simplex (EBS) subtype has been well-characterized genetically.
EBS refers to a group of rare genetic disorders caused by blister formation within the epidermis. The clinical features of all forms of EBS manifest with skin blistering. Palmoplantar-keratoderma, nail dystrophy and shedding, alopecia and oral involvement are often seen. Excruciating pain and severe impairment in quality of life in EBS patients have been reported (Fine et al., JAAD June 2014; Horn and Tidman, Clin Exp Dermatol 2002).
Causes of early mortality in EBS patients include infections and protein loss leading to malnutrition, fluid and electrolyte imbalances, and anemia. Patient care has been limited to supportive measures, including wound care, nutritional support, and antibiotics. In 1991, two groups published in Cell and Science independently revealing the first keratin disorder with a genetic basis in humans, EBS. EBS is usually caused by missense mutations in the genes encoding keratin 5 and 14 (KRT5 and KRT14, respectively) leading to a dominant negative effect on the function of normal keratins (Lane et al., J Pathol 2004), resulting in keratin cytoskeleton dysfunction. The prevalence is estimated to be 6 to 30 per 1 million live births (Horn et al., BJD 1997; Fine et al., JAAD 1991; McKenna et al., BJD 1992).
Targeted methods to ease the symptoms of EB are of great clinical interest, and are provided herein.